Protective manifestation of herbonanoceuticals as antifungals: A possible drug candidate for dermatophytic infection

Abstract Background and Aims Fungal dermatophytosis or Tinea is a predominance in about 20%–25% of all total world populations. Dermatophyte infections are mainly caused by fungi belonging to Trichophyton, Epidermophyton, and Microsporum genera along with some other fungi. This epidemiological distribution may change with migration, lifestyle, immunosuppressive state, drug therapy, and socioeconomic conditions. Methods The present review indicated the bioefficacy of herbal and herbonanoconjugate as safe management of fungal dermatophytic infection. Results It also emphasized the action mechanism as fungicidal and fungistatic with different harmful impacts indicating the need for alternative therapeutics. Simultaneously, the herbal and herbonanoconjugate approaches proved better to manage the prevalence of hepatotoxicity, nephrotoxicity, nausea, altered taste, anemia, GI upsets, hair loss, and so forth. due to conventional oral treatment approaches. Conclusion Adoption of the remedial approach can be recommended after preclinical trials' approval as a safe treatment.

thin-medium thick walls and 1-9 septa, 20-60 in number, 4-13 mm apart, and the macroconidia are widely clavate. They are generally plentiful and borne singly or in clusters. To date two species of this genus are known and among which only one is pathogenic that is E. floccosum, Microsporum audouinii is the type of species whose macroconidia is characterized by rough walls which can be verrucose, echinulate, or asperulated (Table 1). Trichophyton sp. has soft and generally narrow walls and when macroconidia are present possession of 1-12 septa. 1 Dermatophytosis is a Tinea infection in addition to the ringworm.
In humans, the classification of Tinea depends on the body part it F I G U R E 1 The schematic way in which dermatophytes enter the host system Like tinea capitis often with deep folliculitis [4] Tinea capitis Roundworm Scalp hair M. canis, T. tonsurans, T. violaceum Noninflammatory lesions characterized by patches of alopecia with scaling and broken hairs. Inflammatory lesions show tender boggy swelling [5] Tinea corporis Ringworm Nonhairy skin of the body Trichophyton mentagrophytes, Trichophyton rubrum, T. violaceum Erythematous scaly annular plaques [6,7] Tinea cruris Jock itch, dhobi itch Nonhairy skin of the groin

| Conventional treatment role of topical antifungals
Topical or oral antifungal medicines, or a combination of both, are used to treat dermatophytosis, depending on the severity and extent of the infection, the location of the illness, and the causative organism. Basic, superficial dermatomycoses, are often regarded as first-line therapy due to their great efficacy and low potential, as well as related undesirable effects. 18 Depending on the site of the infestation, these medications are blended into various vehicle types, such as lotions, creams, sprays, or gels, to aid penetration and efficacy. 31 Then applied to the outer area of the skin, they quickly penetrate the stratum corneum, functioning as fungicidal/fungistatic agents for mycological eradication. Polyene, azoles, and allylamine/benzylamines are the most common antifungal medicines used on the skin (Table 3). Several novel antifungal medications with greater effectiveness and anti-inflammatory properties have lately been launched in India, expanding the arsenal against these chronic dermatoses. 31 Although the data was limited, nafitine (1%) was found to be superior to placebo in terms of mycological cure rates. Azole combinations with corticosteroids were somewhat more successful than azoles alone in terms of clinical cure, but there was no statistically In folklore, such have been used and continue to be utilized as a medication or dietary supplement for a variety of ailments. 37 People's eating habits and lifestyles are changing these days; they are consuming junk food, which increases the risk of numerous ailments. which is dangerous Fungistatic, fungicidal Local irritation, allergic reactions [34] Ketoconazole Hepatotoxicity [19] Miconazole Liver damage, nausea, arrhythmias, pruritus, hyponatraemia, hyperlipidaemia, dyscrasias [34] Azoles (Triazoles)

Fluconazole
Ergosterol production is inhibited, resulting in a decrease in the integrity and activity of fungal cell membranes Fungistatic, fungicidal Hepatic toxicity, increased plasma concentrations of (topical/oral) anaphylaxis, stevens-Johnson syndrome, hypokalaemia, exfoliative skin disorders, agranulocytosis, thrombocytopenia, toxic epidermal necrolysis, adrenal cortex dysfunction [34] Itraconazole Liver function (but hepatotoxicity is milder than ketoconazole, and hypokalaemia with hypertension is caused by corticosteroids with aldosterone-like action accumulating. Nausea, epigastric discomfort, headache, and edema are all symptoms of leukopenia. Causing heart failure in patients who are elderly or on calcium channel blockers [19] Efinaconazole Oral burning, xerostomia, altered taste, minor GI-upset followed by oral ingestion of the drug, allergic reactions Allylamines Naftifine Squalene epoxidase inhibition: activity linked to squalene accumulation's harmful consequences Fungistatic Burning, erythema, dryness, itching [35] Terbinafine It inhibits squalene epoxidation, a key initial stage in the formation of ergosterol, by functioning as a noncompetitive inhibitor of fungal squalene epoxidase Fungistatic, fungicidal Hepatobiliary dysfunction, induction, agranulocytosis, exacerbation of lupus, severe skin reactions [36] Benzylamines Butenafine Interferes with ergosterol production by blocking the enzyme squalene 2, 3 epoxidase, which converts squalene to squalene oxide Fungicide [16] Polyenes Amphotericin B It's an antifungal that's classified as Fungistatic, fungicidal Serum creatinine, complete blood counts, serum magnesium, blood urea nitrogen, serum sodium, serum potassium, liver function test result must be monitored. When it is used with amino glycosides or neuromuscular blockers, prolonged skeletal muscle paralysis [19] Nystatin It's a polyene-based antifungal that exclusively effects on

Candida
Fungicidal GI-upset is common when nystatin is taken orally [19] Herbs have been utilized for medical purposes since the dawn of impact, but they also reduce the health risks associated with synthetic pesticides or fungicides. 44,45 According to the WHO, 70%-80% of the world's population relies on herb plants. 46 64 The efficacy of plant-based phytochemicals in the overall synthesis and structure of nanoparticles and embedded products of specific nanoparticles is highly attractive, as it provides a significant symbiosis between natural sciences and nanotechnology. 65 Synthesis of biosynthetic nanoparticles does not need toxic chemicals therefore it has minimal impact on the environment. The synthesis course is mostly taking place at ambient temperature and under medium pressure. 66 The exploitation of fungi is believed to be potentially interesting as they can resist and bioaccumulate metals and secrete large quantities of enzymes, making it easier to increase the synthesis of nanoparticles. 67 Biological approach has therefore proven cost-effective, easier, and more based on a greener approach. The principles of green chemistry SHARMA ET AL. Honey will be used as a wound healing [50] US 2013/ 0146481 A1 Bioactive compounds derived from theacea plants, as well as manufacture and application methods Possible plant bioactive components The innovation is based on isolated bioactive chemicals To prevent inflammatory behavior, protect skin tissue from UV radiation damage, and normalize skin disorders in mammals [51] US 2013/ 0323337 A1 A regenerative medication based on a novel herbal combination for wound healing Extracts obtained from Curcuma longa, Hamiltonia suaveolens, Glycyrrhiza glabara, Tipha angustifolia, and Azadirachta indica The present invention is based on a novel, synergistic, and effective herbal composition as a regenerative medicine, which includes a combination of therapeutically effective amounts To treat would healing [52] WO 2014/ 147638 Al A natural wound healing matrix with several functions Tulsi and Curcumin fragments are extracts with herbal medicinal values to increase their properties and have herbal medicinal values A multifunctional natural wound-healing matrix is the subject of this invention. A wound bed consisting of a hydrophilic cotton fabric is the basis for the current concept. One side is covered with zwitterionic chitosan with a low molecular weight, which is implanted on top of the silver nanoparticles created To treat would healing [53] US 8,709, 509 B2 A regenerative medication composed of herbs for the treatment of wound healing Extracts obtained from A. indica, G. glabara, C. longa, H. suaveolens, T. angustifolia, and optionally This invention discloses a novel, synergistic, and effective herbal composition as a regenerative medicine that includes a combination of therapeutically effective amounts To treat skin disease [54] EP 2 896 396 A1 Topical wound therapy using an herbal formulation This breakthrough refers to modern herbal blends that may be used topically antimicrobial agents To facilitate wound healing, in the form of an emulsifying agent and a product that contains at least one herbal component with analgesic, antifungal, anti-inflammatory, and antibacterial properties To cure skin and mucosal lesions [55] WO 2019/ 078931 Al Wound-healing dressing with buckwheat honey and bacitracin A synthesis or preparation containing a combination of buckwheat honey and bacitracin The component is gelled in a single encarnation A method for treating acute and chronic wounds and skin disorders, as well as regenerating skin or dermal tissue in a chronic wound, is the most recent invention [56] US 2019/ 0201474 A1 Formulation of herbal oils for topical use and medicinal uses Herbal oil based on Heterophragma roxburghii bark extract Dry gangrene, diabetic gangrene, foot ulcer, wet gangrene, burn wounds, bed sores, snake bite wounds, chronic open wounds, diabetic, and gangrene caused by cellulitis are among the therapeutic conditions for which the disclosed topical herbal oil formulation provides an inexpensive alternative healing therapy The current disclosure is for a topically applied for treating and curing a range of skin disorders and illnesses, as well as all forms of wounds and other therapeutic circumstances linked with diminished human and animal blood flow [57] have gained considerable prominence in this context; they primarily concern the substitution of chemical products and the enhancement or advancement of processes and technologies to minimize or even remove substances that are toxic to health and the environment. 68 Silver Nanopartoicle (AgNPs) plant-mediated synthesis is more In this context, many useful drugs from plants were discovered because of scientific follow-up of well-known plants used in traditional medicine. Plants will continue to be major sources of drug development, especially as the genomic method gains traction, 83 and plants' potential to create medicines has been depleted in recent years. 84

AUTHOR CONTRIBUTIONS
This work was carried out in collaboration with both authors. Sarika Gupta provided guidance during the study conduct, designed the study, performed the statistical analysis, and standardized the protocol. Anusha Sharma wrote the first draft of the manuscript, and managed the analyses of the study through managing the literature searches. Both authors read and approved the final manuscript.